Higher peripheral neutrophil counts are associated with reduced gray matter, enlarged ventricles and more severe symptomatology in patients with first-episode psychosis (FEP), researchers report.

There has been little interest in the possible role of peripheral immune cells in schizophrenia because the blood-brain barrier (BBB) restricts their entrance into the brain. Under certain conditions, however, the BBB may be disrupted and allow peripheral blood cells to enter the brain.

Dr. Christian Stephan-Otto from Parc Sanitari Sant Joan de Deu, in Barcelona, Spain, and colleagues investigated differences in brain volume and blood cell counts in 137 FEP patients and 81 healthy controls.

FEP patients had significantly smaller gray matter volumes and larger ventricles compared with healthy controls. Neutrophil counts were significantly higher in FEP, whereas erythrocyte counts were higher in healthy controls.

In FEP, but not in healthy controls, higher neutrophil counts were significantly associated with smaller gray matter volumes and larger ventricles, the team reports in Schizophrenia Bulletin, online August 10.

Positive and Negative Syndrome Scale scores

Higher neutrophil counts were also associated with higher Positive and Negative Syndrome Scale (PANSS) scores overall and, in subscale analyses, with hallucinatory behavior, suspiciousness/persecution, hostility, disturbance of volition and preoccupation.

The use of medications other than antipsychotics did not affect these associations; the authors did not describe analyses regarding the potential impact of antipsychotics taken by FEP patients, although antipsychotics could raise neutrophil counts, according to earlier research.

"Although the observational nature of this study does not allow us to conclude that neutrophils are causing brain tissue loss," the researchers noted, "neutrophils have been associated with larger infarct volumes after stroke, which is among the few indirect proofs available of brain tissue loss associated with neutrophils in humans."

"These results suggest that the immunological system of patients with schizophrenia and related disorders is dysregulated, and appears to give support to the autoimmune hypothesis," they concluded.

"Neutrophil count is proposed as an indicator of psychosis severity, and may give rise to new therapeutic options addressing neutrophils or the neutrophil immune response," the researchers noted.